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Objectives: Hepatic fibrosis is a complication of hereditary hemochromatosis. The aim of this study was to determine whether the product of the magnitude and duration of hepatic iron exposure is related to the risk of significant fibrosis., Methods: Receiver-operating characteristic curve analysis to determine the utility of hepatic iron concentration (HIC) and age in the diagnosis of low- or high-grade fibrosis was undertaken retrospectively in 60 subjects who had undergone liver biopsy for assessment of hereditary hemochromatosis. A prospective pilot study was then conducted in 10 additional subjects to evaluate utility of magnetic resonance imaging (MRI) measurements of HIC to predict fibrosis., Results: Eighteen subjects had high-grade fibrosis while 42 subjects had low-grade fibrosis. Hepatic iron concentration alone was highly sensitive (100%) but of limited specificity (67%) in diagnosis of high-grade fibrosis. The product of [HIC x age] had a sensitivity and specificity of 100% and 86%, respectively, for diagnosis of high-grade fibrosis. Magnetic resonance imaging measurements also provided accurate assignment of subjects into fibrosis severity groups., Conclusions: Duration of exposure to iron is important in the development of hepatic fibrosis in hereditary hemochromatosis. The product of HIC and age is highly sensitive and specific for diagnosis of high-grade fibrosis and can be obtained using MRI.

Objective: The aim of this study was to evaluate patient compliance with phlebotomy therapy of hemochromatosis-associated iron overload., Methods: We reviewed medical records of white adults with hemochromatosis and iron overload diagnosed during medical care. We defined three elements of compliance: 1) achieving iron depletion (serum ferritin

Objective: The relationship between the degree of iron overload and the presence of cirrhosis has not been clearly established in hemochromatosis. Severe iron overload occurs without cirrhosis and moderate iron overload can occur with cirrhosis. Previous estimates may have overestimated the problem because of the overdiagnosis of hemochromatosis in patients with alcoholic liver disease and chronic viral hepatitis. The objective of this study was to determine if a threshold for hepatic iron concentration leads to the development of cirrhosis in C282Y hemochromatosis., Methods: This study included only hemochromatosis patients who were homozygotes for the C282Y mutation of the HFE gene and had undergone liver biopsy with hepatic iron concentration. Analysis of the thresholds for cirrhosis were determined using receiver operating characteristic (ROC) curve analysis., Results: Data were available on 100 C282Y homozygotes (62 men, 38 women; mean age 51, range 18-74 yr). ROC curve analysis showed an area under the curve for hepatic iron concentration versus cirrhosis of 0.85 (95% CI = 0.75-0.96). The threshold for the prediction of cirrhosis was 283 micromol/g. At that threshold, the sensitivity was 85% and specificity 84%., Conclusions: From this analysis, it appears that a hepatic iron concentration >283 micromol/g is associated with cirrhosis. However, the low sensitivity of this threshold suggests that other cofactors contribute to the development of cirrhosis in hemochromatosis. Early diagnosis is encouraged to initiate iron depletion before the development of cirrhosis.

Objective: Porphyria cutanea tarda (PCT) is commonly associated with iron overload and hepatitis C virus (HCV) infection. Association between hemochromatosis C282Y or H63D mutations and PCT has been observed, although not uniformly, and iron overload is also commonly found in chronic HCV hepatitis. The aim of the present study was to investigate the frequency of C282Y and H63D mutations and HCV infection in Brazilian patients with PCT and their relationship with iron overload., Methods: Twenty-three patients (19 men) aged 39.6 +/- 11.1 yr were studied. All had dermatological lesions of PCT and high levels of urinary uroporphyrin. HCV infection and iron overload were investigated. DNA samples were analyzed for the presence of HFE mutations., Results: The frequency of C282Y was significantly higher in PCT patients than in 278 healthy individuals (17.4% vs 4%, odds ratio = 5.1, 95% confidence interval 1.5-17.6, p = 0.02), whereas no difference was observed regarding the H63D mutation (30.4% vs 31%, odds ratio = 1, 95% confidence interval 0.4-2.4, p = 1). Biochemical tests in PCT patients showed iron overload with transferrin saturation = 47.3 +/- 20.7% and ferritin = 566.8 +/- 425 ng/ml. Fifteen of 23 (65.2%) patients had HCV infection and alcohol ingestion was observed in 17 of 23 (73.9%)., Conclusions: PCT patients exhibited evidence of iron overload, a high frequency of HCV, and an association with C282Y mutation. These data further support the notion that both acquired and inherited factors contribute to the occurrence of PCT, and indicate that screening for C282Y may be justified in PCT patients.

Hepatic parenchymal iron deposition is a well-known complication of chronic hepatic inflammatory states. This can make the differential between chronic hepatitis and hereditary hemochromatosis difficult, however. The case of a 13-yr-old male with chronic hepatitis C and hereditary hemochromatosis resulting in end stage liver disease and the need for orthotopic liver transplantation is described. There has been no previously described case of the coexistence of these two diseases in a pediatric patient, resulting in end stage liver disease. The progression to cirrhosis in a patient of this age suggests a more rapid progression of the combined diseases than with either disease alone.

We report a case of a posttransplant lymphoproliferative disorder (PTLD) which presented in a liver allograft shortly after transplantation. The patient, who had been transplanted because of cirrhosis due to primary hemochromatosis and chronic hepatitis B infection (HBV), developed early recurrent HBV in the graft, and 2 months after transplantation, liver biopsies showed a malignant large-cell lymphoma. The neoplastic cells demonstrated Epstein-Barr virus DNA by in situ hybridization. The patient died 3.5 months posttransplant due to liver failure. At autopsy, the liver showed nodules of malignant lymphoma, massive hepatic necrosis, and iron overload, but no evidence of rejection. This report suggests that the grafted liver can be the site of PTLD in recurrent HBV and hemochromatosis.

The prevalence of cholelithiasis (gallstones or previous cholecystectomy) was evaluated in a series of 500 cirrhotic patients from Northern Italy (329 males and 171 females, mean age 58 +/- 11 (SD) yr and 61 +/- 10 yr, respectively). Cirrhosis was related to chronic alcohol abuse in 180 cases, non-A non-B (NANB) hepatitis in 160, hepatitis B virus (HBV) in 94 (including 38 with concomitant alcohol abuse), idiopathic hemochromatosis in 44, and miscellaneous causes in the remaining 22 (including 15 with primary biliary cirrhosis). One hundred and sixteen patients (23.2%) had gallstones, and 31 others (6.2%) had previously undergone cholecystectomy, with an overall prevalence of cholelithiasis of 29.4%. The frequency was similar in both sexes (91/329 males, 27.7% vs. 56/171 females, 32.7%; p = NS), showed a slight increase with age, and differed significantly according to etiology (p less than 0.05), with the highest prevalence in the miscellaneous group and the alcoholics (36.4% and 33.3%, respectively). No significant difference was found in the prevalence of cholelithiasis according to Child's A, B, or C class.

Six men and one woman with mild anemia due to beta-thalassemia trait and major iron overload attributable to concomitant primary hemochromatosis were treated by erythrocytapheresis to remove iron, combined with subcutaneous desferrioxamine in the four cases with greater iron load. Depletion was achieved by iron removal of 4.5-15.1 g after 9-24 months' treatment. No side effects were observed, suggesting that such a regimen is effective and safe in this particular subgroup of hemochromatotics.

Biochemical indexes of bone metabolism, bone mineral density, and histomorphometry were evaluated in 14 male patients with noncholestatic cirrhosis due to primary hemochromatosis (six cases) or to chronic alcohol abuse (eight cases), and in 30 male controls of similar age. Alkaline phosphatase in alcoholic patients was significantly higher than in controls (mean +/- SD 50.4 +/- 33.7 vs 33.0 +/- 7.1 U/L, p less than 0.01), as was urinary hydroxyproline in both hemochromatotics and alcoholics (mean +/- SD, 44.3 +/- 8.4 and 40.4 +/- 16.8, respectively, vs 30.1 +/- 4.5 mg/g, p less than 0.001 and p less than 0.005). Bone mineral density was significantly lower in hemochromatotics than in alcoholics and controls (mean +/- SD, 591 +/- 90 vs 765 +/- 87 and 759 +/- 34 mg/cm2, respectively, p less than 0.005 and p less than 0.001). At bone biopsy, trabecular osteoporosis was observed in two hemochromatotics and four alcoholics, and osteomalacia was seen in another alcoholic. Overall densitometric and histomorphometric findings indicate a derangement of trabecular bone in both alcoholic and hemochromatotic cirrhosis, whereas cortical osteoporosis seems limited to hemochromatotic patients.